Project Summary/Abstract Anaplastic large cell lymphoma (ALCL) is an aggressive systemic T-cell lymphoma. ALCL tumors are characterized by distinct expression of CD30 proteins on the cell surface and abnormal expression of the anaplastic lymphoma kinase (ALK) gene due to chromosomal translocations. Expression of the ALK gene has been demonstrated to be a key pathogenic factor for ALCL development. The current standard treatment for ALCL is a multi-drug chemotherapy regimen, which is neither tumor cell- nor tumor gene-specific, and thus, can cause severe side effects. In addition, no imaging technique specific for in vivo detection and monitoring of ALCL tumors has been developed. In this study, we will take advantage of the CD30 surface biomarker and the abnormal ALK gene expression in ALCL tumor cells to develop a 'bifunctional nanomedicine'for both specific treatment and in vivo imaging of ALCL tumors using nanotechnology. To achieve this goal, we will 1). Assemble a bifunctional nanomedicine for specific treatment and in vivo imaging of ALCL;2). In vitro validate the selective ALCL cell binding, specific ALK gene silencing, and cellular effects of the bifunctional nanomedicine;3). Test the in vivo imaging of ALCL tumors by the bifunctional nanomedicine;and 4). In vivo study the therapeutic effects of the bifunctional nanomedicine on ALCL tumors. The development of this bifunctional nanomedicine should provide a new treatment specific for ALCL tumors with no toxicity to normal tissues. In addition, it should enable physicians to in vivo image ALCL tumors and monitor therapeutic responses in a real-time manner. PUBLIC HEALTH RELEVANCE: Project Narrative Anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma. Current challenges in ALCL management include the lack of specific imaging detection methods and specific therapeutic agents. To address these challenges simultaneously, we will develop a novel bifunctional nanomedicine that is tumor cell-selective and tumor gene-specific for ALCL. Our proposed study is extremely important in fighting ALCL, because the development of this bifunctional nanomedicine should provide a new treatment specific for ALCL tumors with no toxicity to normal tissues. In addition, it should enable physicians to in vivo image ALCL tumors and monitor therapeutic responses in a real-time manner.